Niclosamide ethanolamine prevents muscle wasting by inhibiting p38 MAPK-FoxO3a activation in mice exposed to doxorubicin

被引：0

作者：

Zhan, Hongyue ^{[1
,3
]}

Wang, Menghua ^{[1
]}

Han, Pengxun ^{[1
]}

Yu, Xuewen ^{[2
]}

Wang, Yao ^{[1
]}

Weng, Wenci ^{[1
]}

Yuan, Changan ^{[1
]}

Li, Yuyan ^{[1
]}

Wang, Taifen ^{[1
]}

Shao, Mumin ^{[2
]}

Sun, Huili ^{[1
]}

机构：

[1] Guangzhou Univ Chinese Med, Clin Med Coll 4, Shenzhen Tradit Chinese Med Hosp, Dept Nephrol, 1 Fuhua Rd, Shenzhen 518033, Guangdong, Peoples R China

[2] Guangzhou Univ Chinese Med, Clin Med Coll 4, Shenzhen Tradit Chinese Med Hosp, Dept Pathol, 1 Fuhua Rd, Shenzhen 518033, Guangdong, Peoples R China

[3] Shantou Hosp Tradit Chinese Med, Dept Crit Care Med, Shantou, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2020年 / 13卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Niclosamide ethanolamine salt; muscle wasting; doxorubicin; p38; MAPK; FoxO3a; MITOCHONDRIAL; CHEMOTHERAPY; CACHEXIA; KIDNEY;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Introduction: Doxorubicin-induced skeletal muscle wasting is common clinically, and its side effect seems to be associated with patient prognosis. Approaches to preventing skeletal muscle wasting are currently limited. Niclosamide ethanolamine (NEN) can restore body weight and can counteract the side effects of doxorubicin on the kidneys. However, the protective effects of NEN on skeletal muscle have not been investigated. The purpose of the present study was to investigate the protective effects of NEN on the muscles of mice exposed to doxorubicin and their underlying mechanisms. Materials and methods: Male BALB/c mice were used to induce an animal model through a single intravenous injection of doxorubicin and then the mice were randomly assigned to a control (CTRL) group, a doxorubicin group, and a doxorubicin+NEN group. Mice from the doxorubicin+NEN group were fed regular chow supplemented with 2 Wkg NEN in their diet. After two weeks of treatment, muscle strength, running ability, muscle weight, fiber cross-sectional area, fiber type distribution, and the ultrastructure of the muscles were evaluated to verify the protective effects of NEN. Results: With two weeks of treatment, our experiment found that NEN strengthened the muscle force and improved the mice's running endurance. It increased the mass of TA, EDL, and GAs muscle significantly. NEN also alleviated the muscle morphological alterations. It restored the fiber cross-sectional area and thickened the Z-lines of sarcomere. NEN might shift the fibers from type II to type I which might increase mitochondria biogenesis. Moreover, NEN inhibited the p38 mitogen-activated protein kinases (p38 MAPK) and forkhead class O 3a (FoxO3a) activation in the muscles of mice exposed to doxorubicin. Conclusion: This study provides initial evidence that NEN protects the muscles of mice exposed to doxorubicin. The mechanisms might be associated with its inhibition of p38 MAPK-FoxO3a activation.

引用

页码：440 / 449

页数：10

共 28 条

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